Surgical correction of spinal deformities such as scoliosis typically requires fusion of several spinal motion segments. Although this procedure corrects the deformity, it is highly invasive and also severely reduces the flexibility of the spine. Vertebral body tethering or stapling are alternatives that can preserve spinal motion, but require highly invasive surgical procedures in order to achieve the desired correction.
State of the art devices for correction of spinal deformities typically include large assemblies of bone screws connected by cylindrical rods that are implanted posteriorly through the pedicles, or anteriorly on the lateral aspect of the vertebral bodies. Newer correction systems include interconnecting elements between the rod and the screw that allow relative motion between the rod and the screw, effectively allowing the spine to grow without removing the implants. However, the more recent motion-preserving designs are not appropriate for patients who have reached skeletal maturity. Staple and tether systems have been described for mechanically halting progression of the spinal deformity on the concave side of the curve. Several prosthetic disc devices have been described for replacing a diseased intervertebral disc, but these are not designed to correct spinal deformity. Therefore, there is a need for a minimally invasive spinal deformity correction system.
Bone growth during childhood and adolescence requires the coordinated and continuous proliferation and differentiation of chondrocytes in the growth plate. Sandwiched between the primary and secondary centers of ossification of bones, the growth plates are polarized, with resting cells nearest the epiphyseal bone, a zone of proliferation, a zone of hypertrophy and differentiation, and a zone of apoptosis where the cartilage cells die and are replaced by osteoblasts. (Ballock R T, O'Keefe R J. Physiology and pathophysiology of the growth plate. Birth Defects Res Part C Embryo Today 2003; 69(2):123-43.) The continuous passage of new chondrocytes from the resting zone through these strata is responsible for longitudinal bone growth (van der Eerden B C, Karperien M, Wit J M. Systemic and local regulation of the growth plate. Endocr Rev. 2003; 24(6):782-801. Kronenberg H M, Developmental regulation of the growth plate. Systemic and local regulation of the growth plate. Nature 2003 May 15; 423(6937):332-6. Rabie A B, Tang G H, Xiong H, Hagg U. PTHrP regulates chondrocyte maturation in condylar cartilage. J Dent Res., 2003; 82(8):627-31. Schipani E, Provot S. PTHrP, PTH, and the PTH/PTHrP receptor in endochondral bone development. Birth Defects Res Part C Embryo Today, 2003; 69(4):352-62). Defects in coordinated and continuous proliferation and differentiation of chondrocytes may cause serious skeletal disorders such as scoliosis, where growth becomes asymmetric, resulting in deformities in the spine.
There have been several articles describing the use of growth factors (including BMPs) to initiate bony growth at desired locations. While BMP's stimulate Indian hedgehog (Ihh) production, thus stimulating bone growth (Serra R, Karaplis A, Sohn P. Parathyroid hormone-related peptide (PTHrP)-dependent and—independent effects of transforming growth factor beta (TGF-beta) on endochondral bone formation. J. Cell Biol 1999; 145(4):783-94. Yakar S, Rosen C J, Beamer W G, Ackert-Bicknell C L, Wu Y, Liu J L, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002; 110(6):771-81), it is assumed that the local signaling pathways are acted upon by systemic factors, including growth hormone (GH), insulin-like growth factors (IGF's), androgens, estrogens, thyroid hormones, which control overall rates of bone growth. (Schipani E, Provot S. PTHrP, PTH, and the PTH/PTHrP receptor in endochondral bone development. Birth Defects Res Part C Embryo Today 2003; 69(4):352-62).